Isotype-specific regulation of MHC class II genes has been proposed but remains controversial. Reports have suggested that the different class II isotypes may become active at distinct times during cell differentiation and that the regulation of DQ might differ from that of DR and DP. The most convincing examples of isotype-unique class II transcription, however, come from two very interesting CID cell lines have been recently characterized. Each displays a distinct, dyscoordinate pattern of class II gene expression. The general aim of this proposal is to explore the basis of the isotype-specific class Il gene expression in both of these novel cell lines. It is the expectation that results from these studies to clone and characterized isotype-specific transcription factors will provide important insight into deciphering the complexities involving the transcriptional activation of the MHC class II multi gene family.